| Autor: |
Vantaggiato C; Scientific Institute IRCCS E. Medea; Laboratory of Molecular Biology; Lecco, Italy., Clementi E; Unit of Clinical Pharmacology; Department of Biomedical and Clinical Sciences; University Hospital 'Luigi Sacco'; Università di Milano; Milan, Italy., Bassi MT; Scientific Institute IRCCS E. Medea; Laboratory of Molecular Biology; Lecco, Italy. |
| Jazyk: |
angličtina |
| Zdroj: |
Autophagy [Autophagy] 2014 Feb; Vol. 10 (2), pp. 374-5. Date of Electronic Publication: 2013 Nov 26. |
| DOI: |
10.4161/auto.27173 |
| Abstrakt: |
Defective autophagy is associated with neurodegenerative disorders including Alzheimer, Parkinson and Huntington diseases, amyotrophic lateral sclerosis and SCA (spinocerebellar ataxias). Autophagy defects were detected also in SPG49, a complicated form of hereditary spastic paraparesis (cHSP) associated with mutations in the TECPR2 gene, suggesting a role of autophagy also in this heterogeneous group of neurodegenerative diseases. We recently found defective autophagy in SPG15, another HSP subtype associated with mutations in the ZFYVE26/SPG15 gene. Patient-derived cells (fibroblasts/lymphoblasts) carrying different ZFYVE26 mutations show accumulation of immature autophagosomes and increased MAP1LC3B-II and SQSTM1/p62 levels. These findings indicate that ZFYVE26 is a key determinant of autophagosome maturation, which is impaired when the protein is defective or absent. Replication of these findings in primary neurons supports the relevance of defective autophagy in SPG15-related neurodegeneration. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
